As American waistlines continue to expand, a lesser-known obesity-related disease is quickly becoming more common. In fact, in its most serious form, the disease is estimated to become the leading cause for liver transplants by 2020, outpacing even hepatitis C. It's known as nonalcoholic fatty liver disease (NAFLD), an umbrella term for a range of liver conditions that, as the name implies, affects people who drink little to no alcohol yet have more than 5 percent of their liver made up of fat cells. According to the Mayo Clinic, NAFLD affects an estimated 80 million to 100 million Americans.

The more progressive — and therefore more worrisome — form of the disease is known as NASH, or nonalcoholic steatohepatitis. By this stage the disease has progressed to liver inflammation, which can lead to cirrhosis, liver failure and liver cancer — similar to the kind of damage occurring with heavy alcohol use. Dr. Rohit Loomba, chairman of the American Liver Foundation's National Medical Advisory Committee, estimates that about 30 million Americans have NASH.

Like many adverse medical conditions, NAFLD — and especially the more progressive form of the disease — is linked to obesity. Dr. Loomba says that 90 percent of the patients diagnosed with NASH are either overweight or obese. "Obesity and diabetes rates are very high in the U.S. and are also increasing worldwide," he says. "So when we look at the rising rates of NASH in people who don't drink and don't have hepatitis C yet are still developing cirrhosis of the liver, we know something is damaging the liver and we're not containing it."

Perhaps the most alarming aspect of NAFLD, says researchers, is that in its mildest form it typically causes no signs or symptoms, isn't readily picked up in a routine physical, and currently there are no drugs on the market to treat it (although several are in the pipeline).

Dr. Jay Horton, director of the Center for Human Nutrition at UT Southwestern Medical Center, says an individual will typically discover he or she has fatty liver disease if they have a liver function test that comes back abnormal or if they have a scan of their abdomen for some other reason, such as gallstones. "Even though they're finding out about it almost by accident, it's actually very easy to detect excess liver fat with an imaging modality, such as an MRI, CT scan or ultrasound," he says.

Potential cures in the pipeline

To treat the more progressive NASH, pharmaceutical companies such as Pfizer, Bristol-Myers Squibb, Allergan and Novartis are among those currently developing drugs that would potentially reduce the amount of fat in the liver and reverse damage from inflammation and cirrhosis. Despite the fact that it's likely to be three or four years before there's an FDA-approved drug available, Dr. Loomba says finding a cure for fatty liver disease is the "next big frontier" in medical advancements.

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Image of a healthy liver not ravaged by fatty liver disease.

That's because the number of deaths from chronic liver disease and cirrhosis has risen every year since 2007, according to the Centers for Disease Control and Prevention. It is now among the top 15 causes of death for Americans. And with the obesity epidemic showing no signs of abating, demand for drugs to treat fatty liver disease is forecast to remain strong for decades, with the market for a NASH drug estimated to be anywhere from $20 billion to $35 billion.

"Currently, there is no recommendation for genetic testing of fatty liver disease, but someday I believe there will be."-Dr. Jay Horton , director, Center for Human Nutrition at UT Southwestern Medical Center

Despite the potential risks associated with fatty liver disease and the increasing number of people who are developing it, there are currently no official recommendations for routine screening. Dr. Horton says lifestyle changes such as diet and exercise are still the most effective first-line approach for dealing with the disease. "Weight loss works, whether through a bariatric procedure or a strict dietary approach," he says. "Even an 8 percent to 10 percent weight loss seems to improve liver fat."

Dr. Horton says the one underappreciated aspect of the disease is the genetic component. Studies done at UT Southwestern Medical Center show that people with a high-risk variant of a gene known as PNPLA3 were much more likely to have fatty livers if they were obese than if they were not. Once obesity sets in, it's akin to a switch that turns the disease on.

The study also showed that this gene is quite common. He says it's present in about 18 percent of African Americans, 23 percent to 25 percent of European Caucasians; and 49 percent of Hispanics, who are disproportionately affected by fatty liver disease. "Currently, there is no recommendation for genetic testing of fatty liver disease, but someday I believe there will be because this [gene] is a marker for progression," he says.

In the meantime, Dr. Horton's prescription for preventing fatty liver disease is quite simple: "Stay thin," he says. "The key is insulin resistance related to obesity. Anything that helps you to stay thin and have normal insulin sensitivity will prevent this disease."